Illumination unit for fluorescence imaging device

Abstract

An illumination unit (218) for use in a fluorescence imaging apparatus (100) is presented. The illumination unit (218) comprises an excitation source (310) arranged in an alignment member (315) extending radially from an aperture (218h) of the illumination unit (218) for receiving the collection optics of the acquisition unit. The excitation source (310a-310d) of each alignment member is configured to have at least partially different emission characteristics of its excitation light. An imaging head (165) comprising the illumination unit (218) and a fluorescence imaging apparatus (100) comprising the imaging head (165) are also presented. Furthermore, a method of imaging a body part of a patient with a fluorescence imaging device (100), a corresponding computer program and computer program product, and a corresponding surgical, diagnostic and therapeutic method are presented.

Description

Technical Field

[0001] The present disclosure relates to the field of medical equipment, and more specifically, to a fluorescence imaging device. Background Art

[0002] The background of the present disclosure is introduced below by discussing the technology related to its context. However, even when the discussion involves documents, acts, products, etc., it does not imply or represent that the technology discussed is part of the prior art or common knowledge in the field related to the present disclosure.

[0003] Imaging devices are commonly used in several medical applications to provide a visual representation of a patient's body parts, even if they are not directly visible. In particular, fluorescence type imaging devices utilize the phenomenon of fluorescence that occurs in fluorescent substances (called fluorophores), which emit light (fluoresce) when illuminated. An image of a body part (fluorescence image) defined by fluorescence emitted from different locations of the body part then represents the fluorophores present therein. For example, a fluorescent agent (which may be adapted to reach a specific molecule of a desired target (such as a lesion, such as a tumor) and then remain motionless thereon in a fluorescence molecular imaging (FMI) application) can be administered to a patient. The representation of the (motionless) fluorescent agent in the corresponding fluorescence image then facilitates the identification (and quantification) of the corresponding target. This information can be used in several medical applications, for example, in surgical applications for identifying the margins of a lesion to be removed, in diagnostic applications for finding / monitoring lesions, and in therapeutic applications for delineating lesions to be treated.

[0004] To this end, the imaging device is provided with an illumination unit which provides the excitation light necessary to excite the fluorophore of interest (i.e. the fluorescent agent in FMI applications). In order to obtain accurate fluorescence images, it is important to illuminate the field of view of the imaging device as homogeneously as possible (since any changes in its illumination will lead to stray effects in the fluorescence image).

[0005] Lasers can be used in the illumination unit to achieve high illumination homogeneity of the field of view. However, lasers are relatively expensive and bulky and require relatively complex control circuits; moreover, lasers have difficulty in achieving a wide field of view and generate speckle.

[0006] Alternatively, light emitting diodes (LEDs) can be used instead of lasers. LEDs are less expensive, bulky, and complex.

[0007] However, LEDs have relatively low power, so multiple LEDs are required to achieve the illumination intensity necessary to excite fluorophores. Also, the Etendue (the area of ​​the light source multiplied by the solid angle of its illumination pattern) of an LED is generally much greater than the Etendue of a laser.

[0008] Generally speaking, it is difficult to obtain satisfactory field illumination homogeneity using LEDs. This situation is made worse by the fact that it is usually not possible to evenly distribute the LEDs in the lighting unit due to the need to arrange the collection optics (acquisition unit of the imaging device) in the center of the lighting unit.

[0009] At the same time, it is difficult to focus the excitation light of the LED completely towards the field of view. Therefore, a larger area is flooded with the excitation light; this involves a waste of power and can cause additional stray effects in the fluorescence image.

[0010] Furthermore, multiple LEDs hinder the addition of further light sources to the lighting unit. In particular, it is difficult to provide a white light source for illuminating any object present in the field of view to obtain a corresponding reflectance image.

[0011] Likewise, multiple LEDs also hinder the addition of (optical) excitation filters required to limit the frequency band of excitation light. In particular, it is difficult to provide a small-sized excitation filter covering all LEDs, resulting in a corresponding increase in materials and cost.

[0012] US-A-2010 / 193705 describes a device for biochemical analysis of a sample. In particular, two mutually exclusive embodiments are shown. In the first case ( Figure 5 ), two equal excitation light sources tilted toward the sample and completely separate detector systems are arranged on the same side of the sample; in the second case ( Figure 6 A), instead, alignments of excitation light sources with different diffusion angles and imaging sensors are arranged on opposite sides of the sample, both of which are located at the center of the sample.

[0013] WO-A-2020 / 014786 describes a fluorescence imaging device in which radial alignment of LEDs provides light of different colors. US-A-2007 / 024946 describes a hyperspectral / multispectral imaging system in which radial alignment of LEDs provides light of different wavelengths. US-A-2012 / 049089 describes an assembly (having a chamber for receiving an object / sample to be imaged) provided with light sources of different wavelengths that are selectively turned on. Summary of the invention

[0014] In order to provide a basic understanding of the present disclosure, a simplified overview of the present disclosure is given herein; however, the sole purpose of this overview is to introduce some concepts of the present disclosure in a simplified form as a prelude to the more detailed description that follows, and should not be construed as identifying its key elements or delineating its scope.

[0015] In general, the present disclosure is based on the idea of ​​using excitation sources with different emission characteristics.

[0016] In particular, one aspect provides an illumination unit for use in a fluorescence imaging apparatus. The illumination unit includes an excitation source arranged in alignment pieces extending radially from an aperture of the illumination unit for receiving a collection optical device of an acquisition unit. The excitation source of each alignment piece is configured to have at least partially different emission characteristics of its excitation light.

[0017] Another aspect provides an imaging head including an illumination unit.

[0018] Another aspect provides a fluorescence imaging apparatus including an imaging head.

[0019] Another aspect provides a method of imaging a body part of a patient using a fluorescence imaging device.

[0020] Another aspect provides a computer program for implementing the method.

[0021] Another aspect provides a corresponding computer program product.

[0022] On the other hand, a corresponding surgical method is provided.

[0023] On the other hand, a corresponding diagnostic method is provided.

[0024] On the other hand, a corresponding treatment method is provided.

[0025] More specifically, one or more aspects of the present disclosure are set out in the independent claims, and advantageous features thereof are set out in the dependent claims, the wording of all claims being incorporated herein verbatim by reference (reference to any particular aspect providing any advantageous features will apply mutatis mutandis to any other aspect). BRIEF DESCRIPTION OF THE DRAWINGS

[0026] The solution of the present disclosure and further features and advantages thereof will be best understood with reference to the following detailed description, which is given by way of non-limiting indication only to be read in conjunction with the accompanying drawings (where, for simplicity, corresponding elements are denoted by the same or similar reference numerals and explanations thereof are not repeated, and the name of each entity is generally used to indicate both its type and attributes (such as, value, content and representation)). In this regard, it is expressly intended that the drawings are not necessarily drawn to scale (some details may be exaggerated and / or simplified), and that, unless otherwise indicated, they are merely intended to conceptually illustrate the structures and processes described herein. Furthermore, orientation and relative position references (such as front, rear, top, bottom, lateral, etc.) should be understood in relation to the conditions of use of the corresponding entities. In particular:

[0027] Figure 1 shows a diagrammatic representation of a fluorescence imaging device in which a solution according to an embodiment of the present disclosure may be used,

[0028] Figure 2 shows a functional block diagram of an imaging head, in which the solution according to an embodiment of the present disclosure can be implemented,

[0029] Figure 3 shows a schematic representation of a bottom view and a cross-sectional view of a lighting unit according to an embodiment of the present disclosure,

[0030] Figure 4 shows a functional representation of an excitation source alignment member according to an embodiment of the present disclosure, and

[0031] Figure 5-Figure 7 Different examples of experimental results related to solutions according to embodiments of the present disclosure are shown. DETAILED DESCRIPTION

[0032] Special reference Figure 1 , shows a graphical representation of a fluorescence imaging apparatus 100 in which a solution according to an embodiment of the present disclosure may be used.

[0033] The (fluorescence) imaging device 100 is used in medical applications to examine a body part of a patient (not shown) by applying fluorescence imaging techniques, e.g., for diagnostic, therapeutic and / or surgical purposes. For example, the imaging device 100 is used to assist surgeons in performing fluorescence guided surgery (FGS), in particular fluorescence guided resection (FGR) when it comes to tumors.

[0034] The imaging device 100 includes the following components. The trolley 105 accommodates a supply unit 110 and a control unit 115 for supplying and controlling the imaging device 100, respectively. For example, not shown in the figure, the control unit 115 is based on a microprocessor (providing the logic capabilities of the control unit 115), which is associated with a non-volatile memory storing a control program, a volatile memory used as a working memory, and a driver for the corresponding peripheral devices of the imaging device 110. Four casters 120 (only three of which are visible in the figure) are arranged at the corresponding lower corners of the trolley 105 to facilitate moving the imaging device 100 (with a foot brake, not shown in the figure, which is used to fix the imaging device 100 in place). A support 125 extends upward from the rear surface of the trolley 105. The support 125 has a handle 130 for moving the imaging device 100 by its operator. A cantilever 135 extends from the support 125, above the trolley 105. A primary monitor 140 (for displaying images to an operator) and a keyboard with a pointing device such as a mouse or trackball (for inputting information / commands by the operator) are mounted on the boom 135. A pivot arm 150 is mounted on the top of the support column 125 (above the boom 135). An auxiliary monitor 155 (for displaying images to a physician, such as a surgeon) is mounted on the pivot arm 150 (so as to allow it to be rotated in any direction). An articulated arm 160 is also mounted on the top of the support column 125 (near the pivot arm 150). An imaging head 165 (for imaging the body part being analyzed) is suspended from the articulated arm 160. The imaging head 165 is provided with two handles 170 for positioning the imaging head 165 by the operator.

[0035] Reference now Figure 2 , shows a functional block diagram of an imaging head 165, in which a solution according to an embodiment of the present disclosure may be implemented.

[0036] The imaging head 165 is configured to image a scene included in its field of view 203 (defined by the portion of the world within the solid angle to which the imaging head 165 is sensitive). In particular, in the case of a surgical application, the scene involves a patient 206 undergoing a surgical procedure to which a fluorescent agent (e.g., adapted to accumulate in a tumor) has been previously administered. The scene includes a body part 209 of the patient 206 in which a surgical cavity 212 (e.g., a small skin incision in minimally invasive surgery) has been opened to expose a tumor 215 to be removed.

[0037] The imaging head 165 comprises the following components. An illumination unit 218 (described in detail below) is used to illuminate the scene of the field of view 203. In particular, the illumination unit 218 generates excitation light and white light; the excitation light has a wavelength and energy suitable for exciting fluorophores of a fluorescent agent (such as a near-infrared (NIR) type), while the white light appears to be essentially colorless to the human eye (such as containing all wavelengths of the spectrum visible to the human eye, with equal intensity). An acquisition unit 221 is used to acquire a (digital) image of the scene of the field of view 203. The acquisition unit 221 comprises the following components. A collection optical device 224 is received in an aperture 218h of the illumination unit 218 for collecting light from the field of view 203 (in an epi-illumination geometry). The collected light includes fluorescence emitted by any fluorophores present in the field of view 203 (illuminated by the excitation light). In practice, when fluorophores absorb excitation light, they transform into an excited (electronic) state; the excited state is unstable, so the fluorophores decay from this state to the basic (electronic) state in a very short time, thereby emitting fluorescent light (at a characteristic wavelength, which is longer than the wavelength of the excitation light due to the energy dissipated in the excited state as heat), the intensity of which depends mainly on the number of illuminated fluorophores. Moreover, the collected light includes visible light (visible to the human eye) that is reflected (including diffused) by any object (illuminated by white light) present in the field of view 203. The beam splitter 227 splits the collected light into two channels. For example, the beam splitter 227 is a dichroic mirror that transmits and reflects the collected light at wavelengths above and below a threshold wavelength between the spectrum of visible light and the spectrum of fluorescence (and vice versa), respectively. In the (transmission) channel of the beam splitter 227, the fluorescence is defined by the portion of the collected light in its spectrum, and the emission filter 230 filters the fluorescence to remove any residual components outside the spectrum of the fluorescence. A fluorescence camera 233 (e.g., an EMCCD or CMOS type camera) receives the fluorescence from the emission filter 230 and generates a corresponding fluorescence (digital) image, which represents the distribution of fluorophores in the field of view 203. In another (reflection) channel of the beam splitter 227, where visible light is defined by the portion of light collected in its spectrum, reflectivity or photo, a camera 236 (e.g., a CCD or CMOS type camera) receives the visible light and generates a corresponding reflectivity (digital) image, which represents what is visible to the human eye in the field of view 203.

[0038] Reference now Figure 3 , schematic diagrams showing a bottom view and a cross-sectional view of a lighting unit 218 according to an embodiment of the present disclosure.

[0039] In particular, the bottom view shows the lighting unit 218 as seen from the operative side of the imaging head (without any sterile cover that may enclose the entire imaging head), which generally faces downward during the imaging process. The cross-sectional view shows the lighting unit 218 taken along cutting plane AA.

[0040] The lighting unit 218 includes the following components. The base 305 (disc in the example shown in the figure) supports (mechanically) the other components of the lighting unit 218. The base 305 has a through hole (e.g., circular in its center), which defines a hole 218h for receiving a collection optical device of an acquisition unit (not shown in the figure). A plurality of excitation light sources, or simply excitation sources 310, provide excitation light, which has a common wavelength (e.g., 800-2500nm) for all excitation sources 310. In the example shown in the figure, there are 32 excitation sources 310 (such as each excitation source is composed of an excitation LED and a corresponding lens). The excitation sources 310 are arranged in a plurality of alignment pieces 315. The (excitation source) alignment pieces 315 extend radially from the hole 218h in a uniform manner (in a star-shaped configuration), that is, angularly spaced at a constant value. In the example shown in the figure, the excitation source alignment pieces 315 are distributed (uniformly) along a ring in the peripheral area of ​​the base 305. Each excitation source alignment piece 315 includes a plurality of excitation sources 310. In the example shown in the figure, each excitation source alignment element 315 includes four excitation sources 310, identified by reference numerals 310a, 310b, 310c and 310d (such that 32 excitation sources 310 are distributed in eight excitation source alignment elements 315 radially spaced 45° apart).

[0041] In the solution according to the embodiment of the present disclosure, as described in detail below, in each excitation source alignment member 315, the excitation source 310 thereof has at least partially different emission characteristics of the excitation light. For example, the excitation sources 310b and 310c have a higher radiation angle than the excitation sources 310a and 310d.

[0042] The solution mentioned above allows to maintain the optimal arrangement of the collection optics (in particular at the center of the illumination unit) while obtaining a relatively high illumination homogeneity of the field of view (even in the case of a plurality of LEDs with relatively low power and despite their non-uniform distribution). This has a beneficial effect on the quality of the acquired fluorescence images (since it reduces stray effects therein).

[0043] At the same time, the excitation light is focused primarily toward the field of view. This reduces wasted power and additional stray effects in the fluorescence image.

[0044] Specific implementations of the lighting unit 218 according to embodiments of the present disclosure provide additional advantageous effects.

[0045] In particular, the excitation source alignment pieces 315 are equal to each other, i.e., the same number of identical excitation sources 310 are arranged in the same manner (i.e., the same distance from the hole 218h, and the corresponding excitation sources 310a, 310b, 310c and 310d of different excitation source alignment pieces 315 are positioned along corresponding concentric circles that are equal to each other).

[0046] This further improves the illumination homogeneity of the field of view.

[0047] The corresponding (optical) excitation filter 320 covers the excitation source alignment piece 315 (located below it in the figure); the excitation filter 320 limits the frequency band (e.g., in the range of 700-900nm to 2.400-2.600nm) of the excitation light emitted by the corresponding excitation source 310. Each excitation filter 320 is configured as a strip and has a generally rectangular shape; the size of the excitation filter 320 is slightly larger than the occupied area of ​​the corresponding excitation source 310 (4 in the example discussed).

[0048] Thus, the excitation filter 320 can be kept relatively small. This allows reducing the amount of material required for the excitation filter 320 and reducing its cost.

[0049] White light is provided by a plurality of white light sources or simply white sources 325. The white sources 325 are inserted between the excitation source alignment pieces 315 in a uniform manner, i.e., in the middle of each pair of adjacent excitation source alignment pieces 315. In the example shown in the figure, there are 16 white sources 325 (such as each formed by a white LED with a power of 1-3 W and covered by a corresponding lens); the white sources 325 are arranged in groups along the circumference at the center of the ring of the excitation source alignment pieces 315, with each group of 2 white sources 325 close to each other.

[0050] This result is achieved by utilizing the existing space between excitation source alignment members 315. Thus, it is possible to add white light source 325 without increasing the size of illumination unit 218.

[0051] Reference now Figure 4 , shows a functional representation of the excitation source alignment member 315 according to an embodiment of the present disclosure.

[0052] In a specific embodiment, the excitation sources 310a-310d (relative to Figure 3 The excitation sources 310a, 310b, 310c and 310d are each configured to emit excitation light having at least partially different spatial distributions, in particular different radiation angles (upside down). The radiation angle of each excitation source 310a, 310b, 310c and 310d is defined by the corresponding emission cone 405a, 405b, 405c and 405d of the excitation light emitted by it. The boundaries of the emission cones 405a-405d are determined by the position where the irradiance (radiant flux received per unit area) of the excitation sources 310a-310d decreases from its maximum value by a predefined amount (such as -3dB, i.e., approximately 50%). The radiation angle is measured by the half apex angle (half angle) of the emission cones 405a-405d.

[0053] In particular, the excitation sources 310a-310d are mounted on a printed circuit board (PCB) or simply board 410, which physically supports and electrically connects them (e.g., a single board 410 has a ring shape for all excitation source alignment members 315). The emission cones 405a, 405b, 405c, and 405d are symmetrical, with their axes of symmetry being Xa, Xb, Xc, and Xd, respectively, extending perpendicularly to a (common) surface 410s of the board 410 in which the excitation sources 310a-310d are mounted. This significantly simplifies the mounting of the excitation sources 310a-310d on the board 410.

[0054] The (external) excitation sources 310a, 310d (extending from the ends of the excitation light alignment member 315, i.e., located at opposite edges of the excitation light alignment member 315) have an (external) half angle α o The same emission cones 405a, 405d; (inner) excitation sources 310b, 310c (surrounded by outer excitation sources 310a, 310d along excitation light alignment member 315, i.e., inserted between them) have an (inner) half angle α i Same (different from the outer half angle α o ) of its emission cone 405b, 405c; inner half angle α i (strictly) above the outer half angle α o (i.e., α i >α o This provides a symmetrical arrangement of the excitation sources 310 along the excitation source alignment feature 315, thereby reducing any mechanical stress on the board 410 (due to thermal deformation caused by the heat dissipated by the excitation sources 310).

[0055] In particular, the inner half angle α i Preferably the outer half angle α o 1.9-3.1 times, more preferably 2.2-2.8 times, more preferably 2.4-2.6 times, such as 2.5 times. In absolute terms, the inner half angle α i Preferably 16°-28°, more preferably 19°-25°, more preferably 21°-23°, such as 22°, and the outer half angle α o Preferably 3°-15°, more preferably 6°-12°, more preferably 8°-10°, such as 9°. These values ​​have been found to provide optimal results in terms of homogeneity and centrality of the illumination of the field of view.

[0056] For example, the excitation sources 310a, 310b, 310c and 310d include corresponding (excitation) LEDs 415a, 415b, 415c and 415d, respectively (mounted on the board 410 using surface mounting technology). The LEDs 415a-415d are equal to each other (for example, having a power of 0.5-3.0 W, such as 0.8 W in continuous mode, or a power of 1.0-4.0 W, such as 1.7 W in pulsed mode). The LEDs 415a-415d approximate corresponding Lambertian radiators, which emit excitation light with uniform irradiance (radiant flux per unit area per unit solid angle) in all directions. The LEDs 415a, 415b, 415c and 415d are covered by corresponding lenses 420a, 420b, 420c and 420d, respectively (for example, made of silicone). The lenses 420a, 420d of the external excitation sources 310a, 310d are equal to each other, and the lenses 420b, 420c of the internal excitation sources 310b, 310c are equal to each other (and different from the lenses 420a, 420d); the shape of the lenses 420a, 420d is designed to reduce the emission cone 405a, 405d of the corresponding LED 415a, 415d to an outer half angle α o , and the shape of the lenses 420b, 420c is designed to reduce the emission cones 405b, 405c of the corresponding LEDs 415b, 415c to an inner half angle α i This embodiment is particularly simple and cost-effective.

[0057] Additionally or alternatively, the excitation sources 310a-310d emit excitation light having at least partially different radiation intensities (radiant flux per unit solid angle). In particular, the outer excitation sources 310a, 310d emit excitation light having the same (outer) radiation intensity Io, while the inner excitation sources 310b, 310c emit excitation light having the same (inner) radiation intensity Ii (different from the outer radiation intensity Io); (having a lower outer half-angle α oThe external radiation intensity Io of the external excitation source 310a, 310d is (strictly) higher than the internal radiation intensity Ii (i.e., Io>Ii). In particular, the external radiation intensity Io is preferably 1.4-2.3 times, more preferably 1.5-2.1 times, more preferably 1.63-1.94 times, such as 1.78 times, of the external radiation intensity Io. In terms of absolute values, the external radiation intensity Io is preferably 2900-3500 W / sr, more preferably 3000-3400 W / sr, more preferably 3100-3300 W / sr, such as 3200 W / sr, and the internal radiation intensity Ii is preferably 1500-2100 W / sr, more preferably 1600-200 W / sr, more preferably 1700-1900 W / sr, such as 1800 W / sr in continuous mode (in pulsating mode, the external / internal radiation intensities Io, Ii increase by 2.0-3.0 times, such as 2.5 times).

[0058] The difference between the external radiation intensity Io and the internal radiation intensity Ii is mainly due to the outer half-angle α o and internal half-angle α i The difference between the half angles (the smaller the half angle, the higher the radiation intensity). Therefore, this result can be achieved even if all LEDs 415a-415d are of the same type and are supplied with equal or slightly different current intensities; for example, in this case, it is possible to obtain an external radiation intensity Io of 0.55-0.57 W / sr and an internal radiation intensity Ii of 0.59-0.61 W / sr. Alternatively, LEDs 310a, 310d and LEDs 310b, 310c are of different types, and / or a control unit (not shown in the figure) of the imaging device is configured to supply different current intensities to LEDs 415a-41d (higher current intensity for LEDs 415a, 415d and lower current intensity for LEDs 415b, 415c). This further increases the homogeneity of the field of view (such as compensating for system- or device-specific changes).

[0059] As a further improvement, the control unit is configured to correct the fluorescence image to reduce any stray effects of residual non-homogeneity of the illumination of the field of view. To this end, a correction (fluorescence) image is predefined. For example, one or more reference images are provided by acquiring a corresponding infrared image with a (NIR) camera that is sensitive to the wavelength of the excitation light. Each infrared image represents the illumination of the field of view by the illumination unit. In particular, each basic picture element (pixel) of the infrared image has a value that depends on the irradiance of the corresponding position of the field of view. Alternatively, the reference image is provided by acquiring a corresponding fluorescence image of a reference object with homogeneous fluorescence (such as a calibration phantom) with an imaging device (whose illumination unit provides excitation light to the reference object). The correction image is generated by setting each pixel value according to the average value of the corresponding pixel value of the reference (infrared or fluorescence) image, wherein the higher the irradiance of the position, the lower the pixel value of the correction image (for example, inversely proportional to it). For each fluorescence image acquired, the control unit then multiplies the fluorescence image with the correction image (pixel by pixel) before displaying it. In this way, pixel values ​​of fluorescence images with lower illumination are increased and / or pixel values ​​of fluorescence images with higher illumination are decreased to compensate for residual inhomogeneities in the illumination of (at least part of) the field of view.

[0060] Reference now Figure 5-Figure 7 , showing different examples of experimental results related to the solution according to an embodiment of the present disclosure.

[0061] Each figure includes an infrared image generated by the lighting unit, where the darker each pixel is, the higher its irradiance is. Furthermore, each figure includes an (irradiance) graph that plots the irradiance of the lighting unit's field of view versus the distance from its center, with [W / cm 2 ] as the unit, and the horizontal axis is in [mm].

[0062] from Figure 5 Initially, an infrared image 505 and an irradiance map 510 are shown, which are obtained by using the above-mentioned Figure 3 The illumination unit of the structure is obtained, but all the excitation sources are equal to each other, in particular have the same half angle of 9°. In this case, the irradiance at ±70 mm from the center of the field of view is reduced to ~54.5% of its maximum value. Moreover, the distribution of the irradiance shows a donut effect, with a significant depression in the center of the field of view, where the irradiance drops to ~5% of its maximum value (this is caused by the impossibility of evenly distributing the LEDs in the illumination unit, due to the need to arrange the collection optics of its acquisition unit at its center). Therefore, this structure is not advantageous and acceptable, because the illumination performs poorly right in the center of the field of view, i.e., the center of the field of view is actually expected to provide the maximum appropriate illumination.

[0063] Steering Figure 6 , shows an infrared image 605 and an irradiance map 610, which are obtained by Figure 3 The same structure of the illumination unit is obtained, but the third excitation source in each excitation source alignment piece from the center of the illumination unit now has a different half angle of 24°. Figure 5 This provides better illumination homogeneity than the previous example, as the irradiance at ±70mm from the center of the field of view now drops only to ~57.5% of its maximum value. Moreover, the donut effect in the irradiance distribution is essentially eliminated, with the irradiance profile around the center of the field of view at its maximum value of ~19mW / cm 2 Basically flat.

[0064] Steering Figure 7 , showing an infrared image 705 and an irradiance map 710, which are obtained by Figure 3 The same structure of the illumination unit is obtained, but in which the inner excitation sources (the second and third excitation sources from the center of the illumination unit) in each excitation source alignment element now have a different half angle of 24°. Figure 6 This provides better illumination homogeneity than the previous approach, as the irradiance at ±70 mm from the center of the field of view now drops only to ~58.9% of its maximum value. Moreover, the donut effect in the distribution of irradiance is also essentially eliminated in this case, with the maximum value being slightly higher (~19.5 mW / cm2) at the center of the field of view. 2 ), but the irradiance profile around the center of the field of view is not as Figure 6 Medium flat.

[0065] therefore, Figure 6 The structure provides the best lighting distribution (ie, decreasing away from the center and a flat profile at the center), but it requires an asymmetrical arrangement. Figure 7 The structure has a symmetrical arrangement, which provides a good illumination distribution (ie, it decreases further away from the center), but the cross-section in the center is not very flat.

[0066] Revise

[0067] In order to meet local and specific requirements, a person skilled in the art may apply many logical and / or physical modifications and changes to the present disclosure. More specifically, although the present disclosure has been described with a certain degree of particularity with reference to one or more embodiments of the present disclosure, it should be understood that various omissions, substitutions and changes in form and details and other embodiments are possible. In particular, different embodiments of the present disclosure can be practiced even without specific details (such as numerical values) set forth in the previous description to provide a more thorough understanding thereof; on the contrary, well-known features may have been omitted or simplified to avoid unnecessary details that make the description unclear. Moreover, it is explicitly intended that the specific elements and / or method steps described in conjunction with any embodiment of the present disclosure can be combined in any other embodiment as a matter of general design choice. In addition, items presented in the same group and in different embodiments, examples or alternatives should not be interpreted as being in fact equivalent to each other (but they are separate and autonomous entities). In any case, each numerical value should be modified according to the applicable tolerance; in particular, unless otherwise indicated, the terms "substantially", "approximately", "approximately", etc. should be understood to be within 10%, preferably 5%, and more preferably 1%. Moreover, each numerical range should be intended to clearly specify any possible number along the continuous number (including its endpoints) within the range. Ordinal numbers or other qualifiers are used only as labels to distinguish elements with the same name, but they do not themselves represent any priority, precedence or order. The terms "include", "comprise", "have", "includes", "involving", etc. should be intended to have an open, non-exhaustive meaning (i.e., not limited to the listed items), the terms "based on", "depending on", "according to", "function of...", etc. should be intended as non-exclusive relationships (i.e., involving possible other variables), the term "one / an" should be intended to one or more items (unless otherwise explicitly indicated), and the term "component for..." (or any component plus function format) should be intended as any structure suitable for or configured to perform the relevant function.

[0068] For example, an embodiment provides an illumination unit for use in a fluorescence imaging device. However, the fluorescence imaging device may be of any type (see below).

[0069] In an embodiment, the lighting unit has a hole. However, the hole can be of any type (e.g., of any shape and size, arranged in any position, in the center or off-center in the lighting unit, etc.).

[0070] In an embodiment, the hole is used to receive the collection optics of the acquisition unit of the fluorescence imaging device. However, the collection optics can be of any type (see below) and can be received in the hole in any way (e.g., using interference / clearance fit, flush / protruding / recessed, with / without any other components, etc.).

[0071] In an embodiment, the lighting unit includes a plurality of excitation sources. However, the excitation sources may be of any number and of any type (eg, LED-based, LEC-based, etc.).

[0072] In an embodiment, an excitation source is used to provide excitation light for one or more fluorescent substances. However, the excitation light can be of any type (e.g., NIR, infrared (IR), visible light, etc.) for exciting any number and type of fluorescent substances (e.g., any extrinsic / intrinsic or exogenous / endogenous fluorescent substances, such as fluorescers, natural fluorescent components, etc.).

[0073] In an embodiment, the excitation light has a common wavelength. However, the common wavelength may have any value (without excluding the possibility of having additional excitation sources providing excitation light with one or more different wavelengths).

[0074] In an embodiment, the excitation sources are arranged in a plurality of alignment elements. However, the alignment elements can be of any number and any length.

[0075] In an embodiment, the alignment elements extend radially from the aperture in a uniform manner. However, the alignment elements may extend in any manner (e.g., starting from any distance from the aperture, the same or different, down to zero, spaced at any angle depending on their number, etc.).

[0076] In an embodiment, each alignment element includes a plurality of excitation sources. However, each alignment element may include any number of excitation sources (e.g., mounted on a common support or corresponding separate supports, integrated on a common substrate or corresponding separate substrates, spaced evenly or non-evenly along the alignment element, etc.).

[0077] In an embodiment, the excitation sources of each alignment feature are configured to have at least partially different emission characteristics of the excitation light. However, the emission characteristics can be of any number and type (e.g., emission cone, radiation intensity, orientation relative to the support surface, etc.), and they can differ in any way along each alignment feature (e.g., between inner and outer excitation sources, between two or more alternating groups, each group having any number of excitation sources, etc.).

[0078] Further embodiments provide additional advantageous features, but these advantageous features may be omitted entirely in the basic embodiment.

[0079] In an embodiment, the alignment members have a common number of excitation sources. However, this common number may have any value.

[0080] In an embodiment, the alignment elements have a common excitation source arrangement. However, the common arrangement can be of any type (eg, position, spacing, etc.).

[0081] In an embodiment, the alignment elements have a common excitation source configuration. However, the common configuration can be of any type (eg, emission cone, radiation intensity, orientation, etc.).

[0082] In any case, the possibility of having at least partially different alignment elements is not excluded (for example, by maintaining rotational symmetry but evenly distributing some alignment elements with different numbers of excitation sources, such as lack of one or more external excitation sources, different distances from the aperture, different spacings between excitation sources, etc.).

[0083] In an embodiment, in each alignment feature, the excitation source is configured to emit excitation light having at least partially different emission cones. However, the emission cones may be of any type (eg, symmetric / asymmetric, having any radiation angle, etc.).

[0084] In an embodiment, in each alignment element, the excitation source is arranged on a common support surface. However, the support surface can be of any type (e.g., a PCB, a heat sink, etc. for each alignment element or group thereof, up to a single heat sink for all alignment elements, etc.).

[0085] In an embodiment, the emission cones have respective symmetry axes extending perpendicularly to the common support surface. However, the possibility is not excluded that at least parts of the excitation sources are tilted relative to the support surface.

[0086] In an embodiment, in each alignment piece, the excitation source includes one or more inner excitation sources and a plurality of outer excitation sources surrounding the inner excitation sources along the alignment piece. However, the inner / outer excitation sources can be any number and arranged in any manner (e.g., having the same number of outer excitation sources at both ends of the alignment piece, having different numbers of excitation sources at both ends of the alignment piece, etc.).

[0087] In an embodiment, the external excitation source is configured to emit excitation light having an external radiation angle, and the internal excitation source is configured to emit excitation light having an internal radiation angle that is strictly higher than the external radiation angle. However, the external / internal radiation angles can be defined in any way (e.g., at which the irradiance decreases to any portion of its maximum value, at which there is a specific portion of the total radiated power at any point within the radiation angle, etc.) and they can have any value (either relative or absolute).

[0088] In an embodiment, the inner radiation angle is equal to 1.9-3.1 times the outer radiation angle. However, the relationship between the inner radiation angle and the outer radiation angle may be defined in any manner (eg, by their ratio, difference, etc.).

[0089] In an embodiment, the inner radiation angle is 16°-28° and the outer radiation angle is 3°-15°. However, the radiation angle may be defined in any manner (eg, degrees, radiation, etc.).

[0090] In an embodiment, the excitation source includes a corresponding lens defining a corresponding radiation angle. However, the lens can be of any type (e.g., material, shape, etc.); in any case, the possibility of obtaining the same result in different ways is not excluded (e.g., using different lenses for the corresponding excitation source groups, the excitation sources have different structures, etc.).

[0091] In an embodiment, in each alignment element, the excitation source is configured to emit excitation light having at least partially different radiation intensities. However, the radiation intensities may have any values ​​(whether relative or absolute) and may be obtained in any manner (e.g., due to different emission cones of the excitation sources, by supplying different currents and / or voltages to the excitation sources, by providing different structures to the excitation sources, etc.).

[0092] In an embodiment, the internal excitation source is configured to emit excitation light having an internal radiation intensity, and the external excitation source is configured to emit excitation light having an external radiation intensity strictly higher than the internal radiation intensity. However, the internal / external radiation intensity can have any value (either relative value or absolute value).

[0093] In an embodiment, the outer radiation intensity is 1.4-2.3 times greater than the inner radiation intensity. However, the relationship between the outer radiation intensity and the inner radiation intensity may be defined in any manner (eg, by their ratio, difference, etc.).

[0094] In an embodiment, in each alignment feature, the excitation sources include a first number of first external excitation sources, a second number (different from the first number) of second external excitation sources, and one or more internal excitation sources included along the alignment feature between the first external excitation source and the second external excitation source. However, the first / second numbers can be of any type (e.g., having any value (one or more), the number of external excitation sources close to the hole is higher or lower than the number of external excitation sources far from the hole, etc.).

[0095] In an embodiment, in each alignment feature, the excitation source includes a common number of first and second external excitation sources, and one or more internal excitation sources included between the first and second external excitation sources along the alignment feature. However, the common number may be any value (one or more).

[0096] In an embodiment, the excitation source comprises a corresponding excitation LED. However, the excitation LED may be of any type (eg, surface mount / through hole LED, OLED, etc.).

[0097] In an embodiment, the illumination unit includes a plurality of excitation filters corresponding to the alignment pieces. However, the excitation filters can be of any type (e.g., bandpass, low pass, high pass, etc., with any bandwidth, with any shape, of any material, etc.); in any case, the possibility of having two or more excitation filters per alignment piece, each excitation filter for two or more alignment pieces, or even a single excitation filter for all alignment pieces is not excluded.

[0098] In an embodiment, each excitation filter covers the excitation source of the corresponding alignment member. However, each excitation filter can cover the corresponding excitation source in any manner (e.g., by contacting them or a portion thereof, being spaced apart from them, arranging a flat structure above the excitation source, a concave structure at least partially surrounding the excitation source, etc.).

[0099] In an embodiment, the lighting unit comprises a plurality of white light sources for providing white light. However, the white light sources may be any number and any type (eg, the same as or different from the excitation source) for providing any light that does not cause significant excitation of the fluorescent substance.

[0100] In an embodiment, the white sources are inserted between the alignment elements in a uniform manner. However, the white sources may be inserted between the alignment elements in any manner (e.g., with any number of white sources between each pair of adjacent alignment elements, with the white sources between each pair of adjacent alignment elements arranged in any manner (such as radially, circumferentially, etc.), at any distance from the center of the lighting unit, etc.).

[0101] Embodiments provide an imaging head for use in a fluorescence imaging apparatus. However, the imaging head may be of any type (eg, mounted on any support structure, handheld, etc.) for use in any fluorescence imaging apparatus (see below).

[0102] In an embodiment, the imaging head comprises the above-mentioned illumination unit and an acquisition unit. However, the acquisition unit may be of any type (eg based on any collection optics, with or without a reflectivity camera, etc.).

[0103] In an embodiment, the acquisition unit is used to acquire a fluorescence image of the field of view illuminated by the illumination unit. However, the fluorescence image can be of any type (e.g., multi-spectral, monochromatic, etc.) and represent any field of view (e.g., related to any body part to be operated, analyzed, treated, etc.).

[0104] In an embodiment, the acquisition unit has a collection optics that acts through the aperture of the illumination unit. However, the collection optics may be of any type (e.g. based on EMCCD, CMOS, InGaAs, PMT, etc. sensors, with any number and type of lenses, waveguides, mirrors, etc.), and it may act through the aperture in any manner (see above).

[0105] The embodiment provides a fluorescence imaging device. However, the fluorescence imaging device can be of any type (eg, guided surgery equipment, scanner, sample imager, etc.).

[0106] In an embodiment, the fluorescence imaging device includes the above-mentioned imaging head and a control unit for controlling the imaging head. However, the control unit can be of any type (e.g., a microcontroller, a personal computer, etc.) and arranged in any position (e.g., in the central body of the fluorescence imaging device, in the imaging head, etc.).

[0107] In an embodiment, the fluorescence imaging apparatus comprises an output unit for displaying the fluorescence image. However, the output unit may be of any type (eg, one or more monitors, virtual reality glasses, etc.).

[0108] Further embodiments provide additional advantageous features, but these advantageous features may be omitted entirely in the basic embodiment.

[0109] In an embodiment, the control unit is configured to correct the fluorescence image according to a correction image based on the illumination distribution of the illumination unit to the field of view. However, the correction image can be defined in any way (e.g., based on any number of images representing the illumination of the field of view in any way, fixed, generated periodically, at the beginning of each imaging process, etc.), and the fluorescence image can be corrected in any way (e.g., by multiplication, addition / subtraction, convolution operation, etc.).

[0110] In general, similar considerations apply if the illumination unit, imaging head, and fluorescent imaging device each have different structures or include equivalent components, or if it has other operating characteristics (provided it is still within the scope of the claims). In any case, each of its components can be separated into multiple elements, or two or more components can be combined into a single element; moreover, each component can be replicated to support parallel execution of corresponding operations. Moreover, unless otherwise specified, any interaction between different components generally does not need to be continuous, and it can be either direct or indirect through one or more intermediaries.

[0111] The embodiments provide a method for imaging a patient's body part using the above-mentioned fluorescence imaging device in a medical application. However, the method can be used to image any body part (e.g., one or more organs, regions or tissues thereof, etc. in any pathological / healthy condition) and any patient (e.g., human, animal, etc.); moreover, the method can be used in any medical application (e.g., surgery, diagnosis, therapy, etc.). In any case, although the method can facilitate the doctor's task, it only provides intermediate results that can help him / her, but the medical activity in the strict sense is always performed by the doctor himself.

[0112] In an embodiment, the method comprises illuminating the body part (by a lighting unit). However, the body part may be illuminated in any manner (eg, providing only excitation light, white light, etc.).

[0113] In an embodiment, the method comprises acquiring (by an acquisition unit) one or more fluorescence images of the illuminated body part. However, the fluorescence images may be acquired in any manner (eg, alone, together with corresponding reflectance images, etc.).

[0114] In an embodiment, the method comprises displaying (by an output unit) the fluorescence image. However, the fluorescence image may be displayed in any manner (eg, alone, in combination with a reflectance image, in real time, offline, etc.).

[0115] Further embodiments provide additional advantageous features, but these features may be omitted entirely in the basic embodiment.

[0116] In an embodiment, the method comprises correcting the fluorescence image (by the control unit) according to a correction image based on an illumination distribution of the field of view by the illumination unit. However, the fluorescence image may be corrected in any manner (see above).

[0117] In general, the method may be implemented in any way (with the same considerations as described above, which apply analogously to the corresponding steps).

[0118] An embodiment provides a computer program configured to cause the control unit of the above-mentioned fluorescence imaging device to perform the same method when the computer program is executed on the control unit. An embodiment provides a computer program product comprising a computer-readable storage medium implementing the computer program, which can be loaded into the working memory of the control unit of the above-mentioned fluorescence imaging device, thereby configuring the control unit to perform the same method. However, the program can be used on the control unit of the above-mentioned fluorescence imaging device, or more generally on any control unit of any fluorescence imaging device (even of standard type). In any case, the same solution can be implemented with a hardware structure (for example, by an electronic circuit integrated in one or more chips of semiconductor material), or with a combination of software and hardware that is appropriately programmed or otherwise configured.

[0119] The embodiment provides a surgical method, which comprises the following steps. Imaging a body part of a patient with the above-mentioned fluorescence imaging device, thereby displaying a fluorescence image of the body part during a surgical procedure on the patient. Operating on the patient according to the fluorescence image. However, the proposed method can be applied in the broadest sense to any kind of surgical method (e.g., for therapeutic purposes, for preventive purposes, for cosmetic purposes, etc.) and for acting on any kind of (one or more) body parts of any patient (see above).

[0120] The embodiment provides a diagnostic method, which comprises the following steps. The patient's body part is imaged with the above-mentioned fluorescence imaging device, so that a fluorescence image of the body part is displayed during the diagnostic process of the patient. The patient's health condition is assessed based on the fluorescence image. However, the proposed method can be applied in the broadest sense to any kind of diagnostic application (e.g., aimed at discovering new lesions, aimed at monitoring known lesions, etc.) and for analyzing any kind of (one or more) body parts of any patient (see above).

[0121] The embodiment provides a treatment method, which includes the following steps. Imaging a body part of a patient with the above-mentioned fluorescence imaging device, thereby displaying a fluorescence image of the body part during the treatment process of the patient. Treating the patient according to the fluorescence image. However, the proposed method can be applied in the broadest sense to any type of treatment method (e.g., aimed at curing a pathological condition, aimed at avoiding its progression, aimed at preventing the occurrence of a pathological condition, or simply aimed at improving the comfort of the patient) and for acting on any kind of (one or more) body parts of any patient (see above).

Claims

1. An illumination unit (218) for use in a fluorescence imaging device (100), wherein the illumination unit (218) has a hole (218h) for receiving a collecting optical device (224) of an acquisition unit (221) of the fluorescence imaging device (100) and includes a plurality of excitation sources (310) for providing excitation light of one or more fluorescent substances having a common wavelength, the excitation sources (310) being arranged in a uniform manner in a plurality of alignment pieces (315) radially extending from the hole (218h), wherein each of the alignment pieces (315) includes a plurality of excitation sources (310a-310d) configured to have at least partially different emission characteristics of the excitation light.

2. The lighting unit (218) of claim 1, wherein the alignment member (315) has a common number of excitation sources (310a-310d), the excitation sources (310a-310d) having a common arrangement and a common configuration.

3. The lighting unit (218) according to claim 1 or 2, wherein in each of the alignment elements (315), the excitation source (310a-310d) is configured to emit excitation light having at least partially different emission cones (405a-405d).

4. The lighting unit (218) of claim 3, wherein in each of the alignment pieces (315), the excitation sources (310a-310d) are arranged on a common support surface (410s), and the emission cones (405a-405d) have corresponding symmetry axes (Xa-Xd) extending perpendicular to the common support surface (410s).

5. The lighting unit (218) according to claim 3 or 4, wherein in each of the alignment pieces (315), the excitation source (310) comprises one or more inner excitation sources (310b, 310c) and a plurality of outer excitation sources (310a, 310d) surrounding the inner excitation sources (310b, 310c) along the alignment piece (315), the outer excitation sources (310a, 310d) being configured to emit light having an outer radiation angle (α o ) and the internal excitation source (310b, 310c) is configured to emit excitation light with a radiation angle strictly higher than the external radiation angle (α o )'s internal radiation angle (α i ) of the excitation light.

6. The lighting unit (218) of claim 5, wherein the internal radiation angle (α i ) is equal to the external radiation angle (α o ) is 1.9-3.1 times.

7. The lighting unit (218) according to claim 5 or 6, wherein the internal radiation angle (α i ) is 16°-28° and the external radiation angle is 3°-15° (α o).

8. The lighting unit (218) according to any one of claims 3 to 7, wherein the excitation source (310a-310d) comprises a plurality of excitation sources (310a-310d) defining corresponding radiation angles (α i , α o )'s corresponding lenses (420a-420d).

9. The lighting unit (218) according to any one of claims 1 to 8, wherein in each of the alignment elements (315), the excitation source (310a-310d) is configured to emit excitation light having at least partially different radiation intensities.

10. The lighting unit (218) according to claim 9, wherein in each of the alignment pieces (315), the excitation source (310) includes one or more internal excitation sources (310b, 310c) and a plurality of external excitation sources (310a, 310d) surrounding the internal excitation sources (310b, 310c) along the alignment piece (315), the internal excitation sources (310b, 310c) being configured to emit excitation light having an internal radiation intensity (Ii) and the external excitation sources (310a, 310d) being configured to emit excitation light having an external radiation intensity (Io) that is strictly higher than the internal radiation intensity (Ii).

11. The lighting unit (218) according to claim 10, wherein the external radiation intensity (Io) is 1.4-2.3 times the internal radiation intensity (Ii).

12. The lighting unit (218) according to any one of claims 1 to 11, wherein in each of the alignment pieces (315), the excitation source (310d) includes a first number of first external excitation sources (310a), a second number of second external excitation sources (310d) different from the first number, and one or more internal excitation sources (310b, 310c) included between the first external excitation source (310a) and the second external excitation source (310d) along the alignment piece (315).

13. The lighting unit (218) according to any one of claims 1 to 11, wherein in each of the alignment pieces (315), the excitation source (310d) includes a common number of a first external excitation source (310a) and a second external excitation source (310d), and one or more internal excitation sources (310b, 310c) included between the first external excitation source (310a) and the second external excitation source (310d) along the alignment piece (315).

14. The lighting unit (218) according to any one of claims 1 to 13, wherein the excitation sources (310a-310d) include corresponding excitation LEDs (415a-415d).

15. The lighting unit (218) according to any one of claims 1 to 14, wherein the lighting unit (218) comprises a plurality of excitation filters (320) corresponding to the alignment piece (315), each of the excitation filters (320) covering an excitation source (310a-310d) of the corresponding alignment piece (315).

16. The lighting unit (218) according to any one of claims 1 to 15, wherein the lighting unit (218) comprises a plurality of white light sources (325) for providing white light, the white light sources (325) being inserted between the alignment pieces (315) in a uniform manner.

17. An imaging head (165) for use in a fluorescence imaging device (100), the imaging head comprising an illumination unit (218) according to any one of claims 1 to 16 and an acquisition unit (221) for acquiring a fluorescence image of a field of view (203) illuminated by the illumination unit (218), the acquisition unit (221) having a collection optical device (224) that acts through an aperture (218h) of the illumination unit (218).

18. A fluorescence imaging device (100), comprising an imaging head (165) according to claim 17, a control unit (115) for controlling the imaging head (165), and an output unit (140, 155) for displaying a fluorescence image.

19. The fluorescence imaging device (100) according to claim 18, wherein the control unit (115) is configured to correct the fluorescence image according to a correction image based on an illumination distribution of the field of view (203) by the illumination unit (218).

20. A method for imaging a body part (209) of a patient (206) using a fluorescence imaging device (100) according to claim 18 in a medical application, wherein the method comprises: The body part (209) is illuminated by a lighting unit (218), acquiring one or more fluorescent images of the illuminated body part (209) by an acquisition unit (221); and The fluorescence image is displayed by an output unit (140, 155).

21. The method according to claim 20, wherein the method comprises: The fluorescence image is corrected by the control unit (115) according to a correction image based on the illumination distribution of the field of view (203) by the illumination unit (218).

22. A computer program configured to cause a control unit (115) of a fluorescence imaging device (110) according to claim 18 to perform the method according to claim 21 when the computer program is executed on the control unit (115).

23. A computer program product comprising a computer-readable storage medium implementing a computer program, the computer program being loadable into a working memory of a control unit of a fluorescence imaging apparatus according to claim 18, thereby configuring the control unit to perform the method according to claim 21.

24. A surgical method comprising: imaging a body part of a patient using the fluorescence imaging apparatus according to claim 18, thereby displaying a fluorescence image of the body part during a surgical procedure on the patient, and The patient is operated on based on the fluorescent image.

25. A diagnostic method comprising: imaging a body part of a patient using the fluorescence imaging apparatus according to claim 18, thereby displaying a fluorescence image of the body part during a diagnostic procedure of the patient, and The patient's health condition is assessed based on the fluorescent image.

26. A method of treatment, comprising: imaging a body part of a patient using the fluorescence imaging apparatus according to claim 18, thereby displaying a fluorescence image of the body part during a treatment procedure for the patient, and The patient is treated based on the fluorescent image.

Images